The myeloproliferative disorders provide a unique clinical opportunity for following the conversion of prodromal and chronic forms of myeloproliferation into their more aggressive manifestations as seen in acute myeloid leukemia and blast crisis. Utilizing in vitro culture techniques, we propose to study human granulopoietic control mechanisms with the major focus directed toward an understanding of the changes which occur in malignant diseases of the granulopoietic system. In specific terms, we plan to test a hypothesis regarding multiclonal populations in acute leukemia marrow, and study leukemic clones directly for understanding their proliferative characteristics, responsiveness to humoral stimulatory and inhibitory substances, sensitivity to drug therapy, impact on adjacent normal granulocytic clones, and for detecting small mumbers of residual leukemic precursor cells. The recent development of techniques permitting the proliferation of granulocytic clones from human granulocyte progenitor cells in agar and liquid culture, and methods for effectively separating these disparate cell populations by their density distribution patterns allows these studies, and studies evaluating serum colony stimulating factor (CSF) levels to be performed. Clinical correlates will be provided by basing our studies on patient populations being managed according to prospective protocols. To date, the results suggest that clinical benefits may be derived from our studies by anticipating leukemic relapse or evolution, and for devising chemotherapeutic regimens with diminished potential for neutropenic toxicity. Our studies should enable us to evaluate critical factors involved in, and perhaps regulating, the transition from relatively benign to frankly malignant disease states. Parallel studies will be performed in the nonmalignant disorders of granulopoiesis for purposes of comparison and understanding pathogenetic mechanisms underlying these disorders. BIBLIOGRAPHIC REFERENCES: Greenberg, P. L., Bax, I., Levin, J. and Andrews, T.: Humoral and cellular alterations in cyclic neutropenia. Clinical Research, 23:275A, 1975. Greenberg, P. L., Mara, B., Bax, I., Brossel, R. and Schrier, S. L.: Granulopoiesis in the myeloproliferative disorders. Blood 46:1008, 1975.